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• Response to: Five Factors Score in patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss; EGPA): to use or not to use?
  Loic Guillevin
  Published on: 19 November 2013
• Five Factors Score in patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss; EGPA): to use or not to use?
  Sergey V Mooiseev
  Published on: 28 October 2013

• Published on: 19 November 2013

  Response to: Five Factors Score in patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss; EGPA): to use or not to use?

  • Loic Guillevin, Professor
  • Other Contributors:
    • Maxime Samson

  Dear Editor,

  Moiseev and Novikov's comments on the Five-Factor Score (FFS) for eosinophilic granulomatosis with polyangiitis (EGPA) provide the opportunity to address the contribution of scores and their use. The FFS was designed to evaluate necrotizing vasculitis prognosis and identify manifestations associated with death: those are its only roles. Its strength is its validation on 1,108 patients with differen...

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  Dear Editor,

  Moiseev and Novikov's comments on the Five-Factor Score (FFS) for eosinophilic granulomatosis with polyangiitis (EGPA) provide the opportunity to address the contribution of scores and their use. The FFS was designed to evaluate necrotizing vasculitis prognosis and identify manifestations associated with death: those are its only roles. Its strength is its validation on 1,108 patients with different vasculitides, including 230 with EGPA, ie, sufficient to validate its use.1,2 Saying that only cardiac involvement in FFS applies to EGPA is erroneous. Although a concomitant atherosclerotic process cannot be excluded, each patient's cardiac symptoms were reviewed to confirm that they were EGPA- related and not attributable to preexisting atherosclerosis or valvulopathy.1,2 Because the FFS was not designed to predict vasculitis impact on function, peripheral neuropathy was not included. Alveolar hemorrhage was mostly minor, thus not associated with death. That does not mean that severe alveolar hemorrhage cannot be life-threatening; indeed, it is often associated with renal failure, which is an FFS item independently predictive of mortality.1,2
  The second aspect of building scores is how to use them. We worked for a decade on adapting treatment to disease severity and using the FFS to identify patients with poorer prognoses. Moiseev and Novikov's comment on therapeutic choices is inaccurate because many patients studied by Comarmond et al had participated in prospective trials and received immunosuppressant(s) based on their FFS.3-5 Furthermore, the FFS now includes age, thereby emphasizing the severity of vasculitis in the elderly. We agree with Moiseev and Novikov that CORTAGE trial results will probably influence our future therapeutic strategies.6
  Comparing previously reported results, among the 348 patients followed by Comarmond et al,4 55.9% initially received corticosteroids and immunosuppressant(s) (70.8% throughout follow-up), with 25.3% relapse and 88.9% 5 year overall survival rates; whereas Moosig et al's7 269 patients more frequently received immunosuppressant(s) (cyclophosphamide for 71%), with 14% major relapses and 28% minor relapses (comparable to the former) and 97% 5-year overall survival. Azathioprine's steroid-sparing effect and prevention of EGPA relapses are currently under investigation (ClinicalTrials no. NCT00647166), and results should be available in late 2014. ANCA were not retained as a poor-prognosis factor.1,2 However, cardiac involvement, an FFS item, is more frequent in ANCA-negative EGPA patients.4 The authors probably confused the prediction of mortality and relapses, as the latter are more frequent in ANCA positive patients.4,8 However, relapses, even severe, are not associated with higher mortality.8
  Our recently published long term analyses8 of Ribi's et al's patient population5 demonstrated the accuracy of a therapeutic strategy based on distinguishing between EGPA patients with baseline FFS=0 or higher. Indeed, the long-term analysis showed comparable overall and disease free survival rates for FFS=0 and FFS?1 EGPA patients given FFS-guided treatment.
  Certainly, a score is an evolving concept that should consider clinical, immunological and therapeutic items. Based on prospective trial results, we tried to determine factors predicting vasculitis-prognosis severity and optimal treatments. The FFS, which represents part of this effort, will continue to mature, but must remain simple and easy to use in clinical practice, thereby limiting subtleties.

  References

  1. Guillevin L, Lhote F, Gayraud M, et al. Prognostic factors in polyarteritis nodosa and Churg-Strauss syndrome. A prospective study in 342 patients. Medicine (Baltimore) 1996;75:17-28.

  2. Guillevin L, Pagnoux C, Seror R, et al. The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort. Medicine (Baltimore) 2011;90:19-27.

  3. Cohen P, Pagnoux C, Mahr A, et al. Churg-Strauss syndrome with poor- prognosis factors: A prospective multicenter trial comparing glucocorticoids and six or twelve cyclophosphamide pulses in forty-eight patients. Arthritis Rheum 2007;57:686-93.

  4. Comarmond C, Pagnoux C, Khellaf M, et al. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): clinical characteristics and long-term followup of the 383 patients enrolled in the French Vasculitis Study Group cohort. Arthritis Rheum 2013;65:270-81.

  5. Ribi C, Cohen P, Pagnoux C, et al. Treatment of Churg-Strauss syndrome without poor-prognosis factors: a multicenter, prospective, randomized, open-label study of seventy-two patients. Arthritis Rheum 2008;58:586-94.

  6. Pagnoux C, Quemeneur T, Ninet J, et al. Treatment of systemic necrotizing vasculitides in patients ? 65 years old: Results of the multicenter randomized CORTAGE trial. Presse Med 2013;42:679-80.

  7. Moosig F, Bremer JP, Hellmich B, et al. A vasculitis centre based management strategy leads to improved outcome in eosinophilic granulomatosis and polyangiitis (Churg-Strauss, EGPA): monocentric experiences in 150 patients. Ann Rheum Dis 2013;72:1011-7.

  8. Samson M, Pu?chal X, Devilliers H, et al. Long-term outcomes of 118 patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) enrolled in two prospective trials. Journal of autoimmunity 2013;43:60-69.

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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• Published on: 28 October 2013

  Five Factors Score in patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss; EGPA): to use or not to use?

  • Sergey V Mooiseev, MD
  • Other Contributors:
    • Pavel Novikov

  Dear Editor,

  In the excellent study recently published in the Annals of the Rheumatic Diseases [1] F.Moosig et al. evaluated the individualized and more aggressive strategy of immunosuppressive treatment in 150 patients with EGPA. Over the last decade we utilized the same approach in our cohort of 117 patients with EGPA. For induction of remission the authors used cyclophosphamide in patients not only with Five Fac...

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  Dear Editor,

  In the excellent study recently published in the Annals of the Rheumatic Diseases [1] F.Moosig et al. evaluated the individualized and more aggressive strategy of immunosuppressive treatment in 150 patients with EGPA. Over the last decade we utilized the same approach in our cohort of 117 patients with EGPA. For induction of remission the authors used cyclophosphamide in patients not only with Five Factor Score (FFS) of 0 but with other organ- or life-threatening manifestations, e.g. active peripheral nervous system involvement, alveolar haemorrhage or severe eosinophilic alveolitis. FFS was developed in 1996 as a predictor of poor prognosis in patients with systemic vasculitides [2]. It was revised in 2009 [3]. FFS was used in several trials performed by French Vasculitis Study Group as a guide to choosing the strategy of initial treatment in EGPA patients (only corticosteroids if FFS=0 and addition of cyclophosphamide if FFS?1). In our opinion such simplified approach is incorrect, at least partly, for the following reasons.

  First, FFS is not specific for EGPA as it was developed in the heterogeneous group of patients with different vasculitides. In fact only one item of FFS is applicable to EGPA (cardiac disease). Thus, FFS does not account for common and clinically significant manifestations that probably cannot predict survival but can impair response to corticosteroid treatment and lead to disability (e.g. peripheral nervous system involvement). It should be also noted that cardiac disorders in middle- aged patients with EGPA may be due to accelerated atherosclerosis.

  Second, FFS may be misleading. C.Comarmond et al [4] calculated FFS in the cohort of 383 patients with EGPA. The estimated original score was 0 in 76.0% of patients while revised FFS had the same value in only 25.6% of patients. It means that in the latter case three times more patients would require cyclophosphamide for initial treatment. One of the items included in the revised FFS is age older that 65. Thus, every elderly patient with EGPA has FFS of at least 1 and should be treated with cyclophosphamide. Is age really more important than certain relatively rare but life- or organ- threatening visceral manifestations, e.g. severe kidney or lung disease? Systemic necrotizing vasculitides are associated with a high mortality rate in the elderly. But age itself apparently cannot justify more aggressive treatment (at least prior to publication of CORTAGE or similar studies) taking into account higher risk of serious side effects of corticosteroids and immunosuppressants in the elderly patients.

  Third, in the above mentioned French Vasculitis Study Group Cohort the presence of ANCA was associated with the higher risk of vasculitis relapses (35.2% versus 22.5% in ANCA-negative patients, P = 0.01) and the lower risk of death (5.6% versus 12.5%, P < 0.05) [4]. EGPA phenotype is not an item of FFS though its predictive value deserves evaluation in the further studies.

  Fourth, in C.Ribi et al. study [5] 42% of EGPA patients with FFS = 0 failed to respond to corticosteroid therapy or relapsed during corticosteroid dosage tapering or after termination of therapy (peripheral neuropathy and cutaneous lesions were present respectively in 37% and 27% of these patients). Meanwhile in F.Moosig et al. study the rate of major relapses in the whole cohort of patients was apparently lower (14%).

  We do not challenge the predictive value of FFS but the revised score should be revised again to be useful as a predictor of response to immunosuppressive treatment in EGPA patients. Is it really necessary to calculate any score to choose the best treatment in vasculitis patient? Or maybe common sense, clinical judgement and clinical experience are better? Real life is not clinical trial. Scales and scores are important for evaluation of strategies of treatment but they cannot account for all challenges that rheumatologist faces in clinical practice.

  References

  1. Moosig F, Bremer JP, Hellmich B, et al. A vasculitis centre based management strategy leads to improved outcome in eosinophilic granulomatosis and polyangiitis (Churg-Strauss, EGPA): monocentric experiences in 150 patients. Ann Rheum Dis 2013;72:1011-7.

  2. Guillevin L, Lhote F, Gayraud M, et al. Prognostic factors in polyarteritis nodosa and Churg-Strauss syndrome: a prospective study in 342 patients. Medicine (Baltimore) 1996;75:17-28.

  3. Guillevin L, Pagnoux C, Seror R, et al. The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort. Medicine (Baltimore) 2011;90:19-27.

  4. Comarmond C, Pagnoux C, Khellaf M, et al. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): clinical characteristics and long-term followup of the 383 patients enrolled in the French Vasculitis Study Group cohort. Arthritis Rheum 2013;65:270-81.

  5. Ribi C, Cohen P, Pagnoux C, et al. Treatment of Churg-Strauss syndrome without poor-prognosis factors: a multicenter, prospective, randomized, open-label study of seventy-two patients. Arthritis Rheum 2008;58:586-94.

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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